Approximately 25% of the adult US population are current smokers, and although many try to quit, most fail. As an alternative, some smokers use potentially reduced exposure products (PREPs). However, prior harm reduction products, such as light cigarettes, have proven to be a public health disaster. Carcinogen exposure studies and epidemiologic data show that compensatory smoking behavior can make light cigarettes as harmful as regular cigarettes. Therefore, it is important to understand how people use PREPs and to assess how this relates to their harm exposure. Quest(r) cigarettes are a new PREP that uses genetically modified tobacco to provide a "step-down approach to becoming nicotine-free" by marketing cigarettes with progressively lower levels of nicotine: 0.6 mg, 0.3 mg and 0.05 mg. The primary aim of the study is to investigate the effect of progressive decreases in cigarette nicotine level on smoking topography and harm exposure measures. The study will be a within-subject, open-label design of 210 smokers not currently interested in quitting. Participants will be randomized to one of three conditions: 1) continue to smoke their own brand (control); 2) smoke Quest(r) cigarettes in the step-down order, progressively decreasing cigarette nicotine level from 0.6 mg, to 0.3 mg, to 0.05 mg (Quest(r) step-down); or 3) smoke Quest(r) cigarettes in a non-step down random order, counter balanced across subjects (Quest(r) non-step- down). The study will consist of four stages beginning with a 5-day own brand cigarette smoking phase for all participants, followed by one of the three cigarette conditions. For those smoking Quest(r) cigarettes, cigarette nicotine level will change every 10 days, either in a step-down or random fashion. The primary behavioral outcome is smoking topography; specifically total and mean puff volume, which will be assessed at each session. Carbon monoxide to assess smoke exposure, and urinary biomarkers, will also be assessed. At baseline, participants will view Quest(r) advertisements and complete a survey of product expectations to determine the impact of beliefs about Quest(r) cigarettes on subsequent smoking behavior. This study has several important public health implications. It will determine how a new PREP is actually used. It will also determine how product use relates to harm exposure. Finally, it will identify those most susceptible to changes in smoking topography that may increase harm exposure. [unreadable] [unreadable] [unreadable]